The transcription factor NF-κB is considered to be related to various diseases such as ischemic, inflammatory and autoimmune diseases, and it is expected that administration of its decoy will be effective in the therapy and prophylaxis of such diseases (WO 96/35430). The transcription factor NF-κB is a heterodimeric complex of p65 and p50 proteins. This factor usually exists in the form of a complex with the inhibitor protein IκB in the cytoplasm and, as such, is prevented from migrating to the nucleus. However, when exposed to a stimulus such as cytokines, ischemia or reperfusion for whatever reason, the IκB is phosphorylated and hydrolyzed so that the NF-κB is activated and finds its way into the nucleus. NF-κB binds to the NF-κB binding sites on the chromosomes and promotes transcription of the downstream genes. The genes regulated by NF-κB include but are not limited to those encoding cytokines such as IL-1, IL-6, IL-8 and adhesion factors such as VCAM-1 and ICAM-1.
Meanwhile, with regard to encephalopathy, it is known that brain disorders occur from various causes including neuronal death and, therefore, the need for brain-protection has been felt in recent years.
For example, the success rate in the treatment of subarachnoidal hemorrhage originating from a ruptured cerebral aneurysm has increased dramatically since the advent of the operating microscope made aneurysmal clipping a safe operation. However, as to brain disorders such as the cerebral vasospasm following subarachnoid hemorrhage, the mechanisms of onset remain to be elucidated and no effective therapeutic modalities have been established yet.